Wound Repair and Regeneration最新文献

In vitro tissue-engineered skin models are valuable tools for dermatological research. Yet, they often fail to reproduce the complex interactions among vascular, immune, and cutaneous cells during the wound healing process. In addition, inter-individual variability response remains poorly understood, limiting our knowledge of the genetic and environmental factors that influence wound healing. This study presents a 3D autologous, vascularised, and immunocompetent Tissue Engineered Skin model (aviTES), generated using cells from the same donor to study the wound healing process. The aviTES models were injured using a 2 mm punch biopsy, and wound closure was macroscopically monitored for 7 days in the absence of any stimuli. The re-epithelialisation rate was highly reproducible within the same donor. However, wound closure differed between healthy donors (five distinct donors), highlighting individual variability. Indeed, in most cases, complete re-epithelialisation was observed within 2-4 days, but one did not close completely after 7 days. Immunofluorescence analysis revealed lymphocytes (CD45+/CD3+) migration for all donors, but no migration of CD206-positive cells or neo-angiogenesis into the wound sites. By contrast, platelet lysate treatment promoted epidermal cell migration, capillary organisation/neo-angiogenesis, and altered collagen and MMP secretion at levels that were specific to each donor, highlighting donor-specific responses to treatment. This innovative autologous skin model reproduced several key features of the human wound healing process and may represent a new tool for studying wound healing process and inter-individual variability, paving the way for advances in personalised medicine.

Osteomyelitis of the feet is common in persons living with diabetes due to peripheral artery disease, peripheral neuropathy, and increased susceptibility to infection. Although plain radiography is a low-cost and widely available diagnostic tool, its diagnostic performance is limited. Serial radiography may improve the accuracy and clinical utility. This systematic review studies the diagnostic accuracy, limitations, and clinical utility of singular versus serial plain radiography for diagnosing osteomyelitis in the foot in persons with diabetes at diagnosis and follow-up. We conducted PubMed and Embase searches for articles on the diagnostic performance of serial plain radiography for osteomyelitis of the foot in patients with diabetes. Multiple z-tests were used to compare the performance of singular and serial radiographs. Fourteen studies were included, with only one providing original data on serial radiography. The sensitivity of singular radiography ranged from 22% to 93%, and specificity ranged from 22% to 94%. Serial radiography had a sensitivity of 89% and a specificity of 38%. Of the 13 studies, serial radiography outperformed singular radiography in terms of sensitivity in three reports but failed to outperform singular radiography on specificity in any of the reports. The initial examination indicated little advantage of serial radiography over singular radiography for the diagnosis of diabetic foot osteomyelitis. However, a significant exclusion bias exists due to the lack of research in this area. Further research is warranted to clarify the clinical utility of serial radiography.

Skin organoids are 3D multicellular systems formed through self-organisation in vitro, driving research toward functional-related phenotypic replication from structural mimicry to functionally relevant phenotypic replication. However, this field still faces challenges in improving vascularisation, neurogenesis, and immune integration. This review provides a comprehensive overview of the latest advancements in this field. First, it organises the construction of epidermis-dermis-basement membrane units, vascular/neural/immune modules and accessory organs such as hair follicles, sweat glands, and sebaceous glands into 'component-source-function readout' to highlight key points and clinically relevant endpoints (barrier function, hair growth, sweat gland secretion, and sensation). Subsequently, it outlines the key culture and assembly elements (extracellular matrix composition and mechanics, air-liquid interface, perfusion/organ-on-a-chip and bioprinting) that influence the maturation trajectory of tissues. Then, it compares the differences in plasticity, maturity and accessibility between pluripotent stem cells, adult/primary cells and patient-derived cells. At the application level, it concludes that skin organoids have been used to model inflammation, genetic disorders, infections, and tumours, enabling simultaneous efficacy and safety readouts in drug discovery and toxicology assessment. Translation challenges include vascularisation and perfusion, neurogenesis and sensory function, immune integration, batch consistency and GMP quality, scalability and cost. We propose a staged validation pathway integrating engineering, biology and regulatory considerations, and envision optimisations combining multi-omics, chemoproteomics and artificial intelligence to accelerate the transition from research-grade prototypes to clinical applications.

Minimally invasive floating metatarsal osteotomy has been proposed as a surgical strategy to address recurrent or persistent diabetic foot ulcers (DFUs) by correcting underlying biomechanical deformities. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, querying four databases through September 2025 for studies involving adult patients with neuropathic DFUs treated with minimally invasive floating metatarsal osteotomy and followed for at least 12 months. Six studies comprising 184 subjects (176 with DFUs, 8 prophylactic) met inclusion criteria. Pooled outcomes demonstrated a healing rate of 98% (95% CI: 0.94-1.00) with a mean time to closure of 31.7 days (95% CI: 24.1-39.3). Ulcer recurrence occurred in 4% (95% CI: 0.02-0.09), while transfer lesions developed in 14% (95% CI: 0.08-0.20) and nonunion was observed in 14% (95% CI: 0.06-0.29). The overall infection rate was 7% (95% CI: 0.04-0.12). These findings indicate that minimally invasive floating metatarsal osteotomy is a safe and effective surgical option for off-loading neuropathic DFUs; demonstrating high healing rates, rapid time to closure and low recurrence when compared with conservative care. Larger randomised controlled trials are warranted to validate these results and establish standardised surgical indications.

TGF-β regulates the expression of the α11 integrin, a crucial collagen receptor in wound healing. As healing is impaired in older mammals, we examined the influence of aging on the regulation of TGF-β-mediated α11 integrin expression in gingival repair. Primary cultures of human gingival fibroblasts from young and aged donors were examined by RT-qPCR and Western blot to assess the expression of α2 and α11 integrins, TGF-β (isoforms 1, 2, 3), and TGF-β receptors 1 and 2. TGF-β1 and TGF-β2 were quantified by ELISA. TGF-β activity was evaluated using a gene reporter assay. In gingival wounds created in young and aged mice, collagen deposition and organisation, and expression levels of α11 integrin, TGF-β1 and TGF-β2 were quantified. Data were analysed using unpaired t-test, Mann-Whitney or ANOVA. There were reduced expression levels of α11 integrin (76% mRNA/33% protein) and TGF-β1 (34% mRNA/40% protein), and reduced TGF-β activity (38%) in cultured fibroblasts from older compared with younger donors. Treatment with TGF-β1 induced a 3.6-fold increase of α11 integrin mRNA and a 45% increase of α11 integrin protein in fibroblasts from younger donors, but there was no change in treated cells obtained from older donors. Compared with younger mice, gingival wounds in older mice demonstrated lower levels of collagen deposition (61%), collagen alignment (48%), α11 integrin (77%) and TGF-β1 (86%). Aging is associated with reduced TGF-β1 expression and signalling in gingival fibroblasts, which leads to diminished α11 integrin expression. This disruption of TGF-β1-dependent α11 integrin signalling underpins one potential mechanism for impaired gingival connective tissue repair seen during aging.

Chronic non-healing wounds represent a major clinical challenge, often associated with diabetes, vascular insufficiencies and aging. Despite the substantial burden that such wounds place on patients and healthcare systems, few biomarkers have been approved for prediction of wound healing trajectories and outcomes, limiting opportunities to inform clinical management decisions or quantify patient responses to interventions. Recent advances have identified cell-free nucleic acids as powerful tools for gaining molecular insights because they offer a non-invasive, dynamic snapshot of physiological and pathological processes occurring throughout the body. In particular, cell-free RNAs from non-coding RNA families including microRNA, long non-coding RNA, circular RNA and transfer RNA fragments can be profiled on a large scale to reveal novel disease signatures to support biomarker development. The presence of such non-coding RNAs in serum, plasma or other biofluids provides a rich resource for uncovering new parameters that can support biomarker development for wound repair. In this review article, we highlight some of the current challenges associated with biomarkers for wound healing in clinical practice. We then survey the microRNAs, long non-coding RNA and circular RNAs landscape in relation to their utility as biomarkers in diabetic foot ulcers and other chronic wounds. Collectively, these extracellular RNAs offer a multifaceted view of wound biology and may serve as non-invasive biomarkers for stratifying wound severity, predicting healing outcomes and guiding personalised interventions.

Hypergranulation in chronic wounds reflects impaired healing, leading to delayed recovery, increased risk of infection and higher treatment costs for healthcare systems. Despite its impact, hypergranulation is often misidentified in the early stages, hindering timely intervention. This study presents a deep learning-based method to distinguish between hypergranulated and non-hypergranulated tissue. The dataset comprised 6235 wound images from Hospital de la Santa Creu de Vic (Catalonia, Spain) and DFUC 2022, with balanced classes. Five architectures were evaluated using transfer learning: ViT, VGG16, RepVGG, MobileViT and RepGhost. RepGhost achieved the best results (81.4% accuracy, 89.4% area under the receiver operating characteristic curve [AUC]), outperforming both CNNs and transformers. Lightweight models (RepGhost, MobileViT) also demonstrated high performance, making them suitable for implementation on mobile devices. This tool may assist clinicians in the early detection of hypergranulation and improve wound treatment outcomes. This appears to be the first deep learning study on this condition to utilise a large, balanced dataset.

Approximately 20% of chronic leg ulcers remain recalcitrant despite treatment of underlying factors and best standard of wound care. This study aimed to evaluate the effectiveness of partial-thickness punch grafting in promoting healing and reducing pain in patients with chronic, hard-to-heal leg ulcers of various causes. In this single-centre, retrospective cohort study, 93 patients were treated between January 2016 and December 2024, with follow-up at 1, 3, 6 and 12 months. The primary outcome was complete wound healing, while secondary outcomes included pain reduction and wound surface changes. At 12 months, 78/88 analysed patients (88.6%) achieved complete healing of the target ulcer. Pain levels improved substantially, with the proportion of pain-free patients increasing from 17.6% at baseline to 76.3% at 6 months. Donor site complications were minimal (6.5%) and cosmetic outcomes were excellent. Recurrence after 12-month follow-up occurred in only 9% of healed ulcers within 12 months. These results confirm that partial-thickness punch grafting is a highly effective and minimally invasive technique for treating hard-to-heal leg ulcers, delivering durable healing, rapid pain relief and low morbidity. This study provides new long-term data supporting the broad clinical utility of punch grafting across diverse ulcer types.

Chronic venous insufficiency and venous leg ulcers remain a major challenge in wound care, with profound effects on patient health and quality of life. This prospective observational study compared clinical outcomes and patient-reported quality of life following conservative or surgical treatment of venous leg ulcers at Miguel Servet University Hospital, Spain, between 2017 and 2021. Fifty-two patients completed baseline and follow-up assessments with the 36-Item Short Form Health Survey and the Charing Cross Venous Ulcer Questionnaire. Conservative therapy was associated with a significantly shorter mean estimated time to healing compared with surgical treatment (average 21.5 vs. 34.1 weeks, p = 0.019) and greater ulcer area reduction (97% vs. 78.9%, p = 0.034) than surgical treatment with skin grafting and autologous fat transfer. Although complete closure rates were higher in the conservative group (66.7% vs. 47.4%), the difference was not statistically significant. Quality of life improvements were greater in the conservative group, with significant gains in bodily pain, general health, vitality and emotional well-being. Multivariate analysis identified smaller ulcer size, fewer comorbidities and conservative treatment as independent predictors of quality of life improvement. Surgical intervention yielded modest benefits, limited to vitality. These findings demonstrate that improvements in quality of life are closely tied to ulcer healing rather than treatment modality. The study underscores the efficacy of compression therapy and highlights the importance of patient-reported outcomes as essential endpoints in the evaluation of venous leg ulcer management.

Recombinant human platelet-derived growth factor BB (rhPDGF-BB), is the only growth factor approved by the US Food and Drug Administration (FDA) for tissue regeneration and rejuvenation indications. It has received four FDA approvals for both soft tissue (e.g., skin) and hard tissue regeneration/rejuvenation. Regranex gel, 0.01% rhPDGF-BB, is the only growth factor approved by the FDA for the promotion of skin wound healing. While the safety of one and two 15 g tubes of Regranex, generally sufficient for up to 60 daily applications onto open skin wounds, has never been questioned, a decade after its introduction in 1997, a boxed warning regarding rates of cancer mortality was placed on its label for daily use of three or more tubes. This was based on a mathematical calculation on incomplete data from an insurance claims database which was subsequently invalidated with the addition of three more years of data. Removal of this warning from the label required another decade and several very large propensity-matched database studies including over 13,000 patients. These studies provided incontrovertible proof that up to 140 daily applications (≥ 4 tubes) of rhPDGF-BB onto open skin wounds are safe, with no increased risk of either cancer development or cancer mortality. Removing a boxed warning is an arduous task that requires extensive and robust evidence; less than 4% of box warnings are removed once placed. Thus, the successful removal of the boxed warning from the Regranex label should reassure both prescribers and patients of the product's safety.